Universal recognition is given to the association between accelerated linear growth, the appearance of sexual characters and eventual closure of the epiphyses in normal puberty. The specific factors that initiate and sustain these processes and their relationship to the emergence of adrenal androgen secretion are obscure. A major objective of the proposed research is to establish by longitudinal study, any distinct temporal relationship which might exist between gonadotropin and gonadal secretion on the one hand, and that of the adrenal androgens on the other. This will be done in individual normal children from pre-to post-puberty. We also wish to define the role of the adrenal androgens in skeletal maturation during puberty, and to assess their role in the emergence of secondary sex characters in the normal female. To help in this aim, patients with various disorders of endocrine function affecting their growth and maturation will also be studied longitudinally. The effects of appropriate hormonal therapy will be monitored as well. From these observations the factors that trigger the maturation of the adrenal at puberty and modulate its androgen secretion may be elucidated. In order to complement our study of the influence of adrenal androgens upon skeletal tissue we will 1) establish a system of bone organ culture in which the effects of the adrenal androgens can be compared to those of the gonadal hormones and 2) assess the importance of hormonal metabolism by the bone rudiments for biologic action.